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Cancer in rodents: does it tell us about cancer in humans?

Vladimir N. Anisimov is Head of the Department of Carcinogenesis and Oncogerontology at the N.N. Petrov Research Institute of Oncology, St. Petersburg. After graduation from the 1st Leningrad Medical Institute in 1968 he joined the Laboratory of Experimental Tumors, renamed the Laboratory of Carcinogenesis and Ageing in 1999. His research interests include the mechanisms of chemical carcinogenesis, ageing as a modifying factor of carcinogenesis, the role of the pineal gland in ageing and cancer, and cancer and premature ageing prevention. He is the author and co-author of many books and papers on carcinogenesis and ageing. Since 1994 he has been the President of the Gerontological Society of the Russian Academy of Sciences.

Svetlana V. Ukraintseva is a senior research scientist at Duke University. Before going to Duke University, she spent several years at the Max Plank Institute in Germany conducting research on cancer epidemiology and the connection between somatic ageing and cancer risk. Her research interests include mechanisms of human ageing and associated pathology, particularly that of cancer; factors favouring the increase in cancer incidence rates in developed countries; the genetics of ageing and cancer; and candidate anti-ageing interventions. She is the author and co-author of many papers addressing the connection between ageing and cancer morbidity and mortality, the origin of centenarians, recent trends in human survival patterns, innovative approaches to genetic studies of ageing, prospective cancer treatments and anti-ageing interventions.

Anatoliy I. Yashin is a research professor at Duke University. He was previously Head of the Advanced Statistical Methods Laboratory at the Max Plank Institute in Germany. His research interests include factors and mechanisms of ageing and ageing related disorders and longevity in humans and laboratory animals. He has authored and co-authored many papers on the connection between cancer and ageing; reproduction and ageing; ageing, mortality and stress resistance; the origin of today's centenarians; recent trends in human survival patterns; and innovative approaches to genetic studies of ageing and longevity.

Subjects

Abstract

Information obtained from animal models (mostly mice and rats) has contributed substantially to the development of treatments for human cancers. However, important interspecies differences have to be taken into account when considering the mechanisms of cancer development and extrapolating the results from mice to humans. Comparative studies of cancer in humans and animal models mostly focus on genetic factors. This review discusses the bio-epidemiological aspects of cancer manifestation in humans and rodents that have been underrepresented in the literature.

Key points

Whereas laboratory rodents (namely mice and rats) are similar to humans in some aspects, there are important differences among mammalian species that make valid interpretation and extrapolation of the results from rodent cancer experiments to humans problematic.

The five most common human cancers are those of the breast (female), the prostate (male), and the lungs, colon, and stomach (both sexes). Mammary tumours are also common in rodents. However, there are no rat or mouse strains that exhibit a high incidence of spontaneous carcinomas of the stomach or colon.

A decrease in the overall risk of cancer owing to old age has been recorded in both human and rodent studies. Three important factors could be responsible for this intriguing decline: detection bias, differential selection, and the effects of individual ageing. Studies in rodents argue against a diagnostic bias as a leading cause.

The risk of cancer has increased over time in most human populations. Why this is remains unclear, but addressing this problem is crucial for understanding the nature of cancer.

Some studies indicate that the differences in cancer incidence rates between males and females are similar in rodents and humans. This is a surprising finding that requires additional explanation.

Whereas tumours often grow at a slower rate during old age, the chances for survival of a transplanted tumour in a recipient host often increases with rodent age. This is in agreement with human data indicating that ageing can both decelerate tumour growth and increase the chances of latent tumour survival in older organisms.

The spontaneous regression of tumours is a rare phenomenon in adult humans, whereas it is common in mature laboratory rodents. This effect and its implications need further investigation.

Few rodent carcinogens were established as clearly carcinogenic to humans. Similarly, some human carcinogens are not carcinogenic to rodents. This creates a significant problem for interpreting the results of animal experiments with carcinogens in relation to humans.

These and other differences warn against the simple extrapolation of the results of rodent experiments to humans and call for further investigation of this important problem to reliably predict cancer risks, as well as foster success in treating human cancers based on data from laboratory animal studies.

The International Agency for Research on Cancer. Cancer Incidence in Five Continents. Volumes 1–8 (Lyon, IARC, 1965–2003).
Important data source on age-specific cancer incidence rates in humans worldwide.

Ukraintseva, S. V. & Yashin, A. I.Individual aging and cancer risk: How are they related?Demogr. Res.9, 163–196 (2003).
A study that establishes a link between somatic ageing and the decline in overall cancer risk at old ages.

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Acknowledgements

The authors wish to thank James W. Vaupel for the opportunity to conduct substantial parts of this work at the Max Planck Institute for Demographic Research, Germany. We are thankful to Mark A. Zabezhinski and Igor Akushevich for their comments on the paper. We are also thankful to Virginia Lewis for help in preparing this manuscript. This research was partly supported by NIH/NIA grants and by a grant from the President of the Russian Federation.

Author information

Affiliations

Department of Carcinogenesis and Oncogerontology, N.N. Petrov Research Institute of Oncology, Pesochny-2, St. Petersburg 197758, Russia.